ESRA History: Important Milestones

Athina Vadalouca,¹ Eleni Moka,²

1.     Pain & Palliative Care Centre, Athens Medical Centre, Athens, Greece

2.     Anaesthesiology Department, Creta Interclinic Hospital, Hellenic Healthcare Group (HHG), Heraklion – Crete, Greece  

To effectively unfold a history, one needs to:

1. know those inspired people, that paved the pathway and «wrote» the history,
2. comprehend their backgrounds and motivations,
3. delve into and understand their scientific or/and intellectual journeys,
4. be one of them to identify and trace the history, or develop a deep connection with the history pioneers, aligning with their objectives and sharing their goals and vision, to authentically convey their perspectives.

Since these criteria are met, the up to now history of the European Society of Regional Anaesthesia and Pain Therapy (ESRA) will be elaborated upon the lecture of Athina Vadalouca, during the 41^st ESRA Annual Congress, held in Prague in September 2024, and will further be summarized in the following pages. 

ESRA was founded 44 years ago. Honouring its history and cherishing its heritage, nowadays, the society represents a dynamic organization that continues to share the passion for advancing education, scientific research and training in Regional Anaesthesia (RA), Perioperative Care and Pain Medicine. While its origins are rooted in Europe, ESRA has evolved into a global network, currently embracing more than 8.000 active voting members and an audience of more than 30.000 trainees, specialists, and nurses across the globe. As an international community, with a reputation for innovation, diversity and inclusion, its mission transcends geographical boundaries, offering invaluable opportunities to medical professionals worldwide, with the promise to support them during the transform of their professional journey.

ESRA was founded by individuals, who shared the same mission, vision and talent to create the society. The idea originated from the first officers of ASRA Pain Medicine and from some brilliant minds who were well acquainted with many people in Europe, both professionally and personally. For instance, Ben Covino worked with Bruce Scott, the first President of ESRA, in Edinburg in 1976, and encouraged him to start establishing a European Society of Regional Anaesthesia.

ESRA was officially founded by a Belgian Royal Decree on January 31, 1980, following intensive efforts and a pivotal meeting in Heidelberg, on September 24-25, 1979. The organization's «Founding Fathers» were Albert Van Steenberge (Belgium), Hans Nolte (Germany), Arno Hollmén (Finland), Bruce Scott (UK), and Françoise Van Steenberge (Albert’s wife), who served as the group’s secretary. They established an administrative and scientific structure, accommodating Europe’s diverse countries, languages, and currencies. 

Under Bruce Scott’s leadership, two committees were created from the very first beginning: one to establish and set up the society across Europe and another to plan the first scientific meeting. This inaugural meeting was held in Edinburgh on September 16–18, 1982. ASRA Pain Medicine provided funding, and several UK companies (Astra Pharmaceuticals Ltd, Duncan Flockhart & Co Ltd, Dupont UK Ltd, and Roche Products Ltd) offered substantial sponsorship. The Edinburgh meeting marked the emergence of ESRA as a separate and distinct entity. The meeting lasted two days, with its scientific activities taking place in only one plenary hall, hosting one session at a time. 

Over the years, the ESRA scientific meetings grew and flourished, now expanding to four days and featuring multiple concurrent sessions, such as networking symposia, plenary experts’ panel discussions, instructional refresher course lectures, PRO–CON debates, «ask the expert» interactive sessions, «second opinion» discussions, «tips & tricks» sessions, problem based learning discussions (PBLD), free papers and video contests, electronic poster presentations with a poster competition, various hands–on clinical workshops on Ultrasound Guided Regional Anaesthesia (UGRA) and Pain Management, cadaver workshops, and exams for the acquisition of the ESRA Diplomas (ESRA–DRA and ESRA–DPM). Many other innovative sessions are introduced on an annual basis, including complex case discussions with audience–submitted content, trainees sessions, LIVE demonstrations on models and the 360 open space simulation courses. The annual congresses are pre–planned well in advance and take place in major European cities, each with unique social programs.

ESRA's first President was Bruce Scott, Albert Van Steenberge held the position of General Secretary, and Otto Schulte–Steinberg took charge of the finances as Treasurer. The initial zones created in 1980 were Benelux, France, Germany, Italy, Scandinavia, Spain, and the UK. Greece became a member in 1988, followed by Austria, Switzerland, and Portugal in 1990. The aim of ESRA was to attract all European countries, by offering educational, training and research opportunities, adhering to a philosophy of inclusivity and knowledge advancement beyond barriers.

ESRA actively supported the establishment of national or regional groups or organisations of RA throughout Europe, inviting and encouraging them to join the society under its rules and regulations. ESRA Ambassadors such as Albert Van Steenberge (Belgium), Slobodan Gligorijevic (Switzerland), Marc Van De Velde (Belgium) and Patrick Narchi (France) have supported and represented Eastern European countries throughout these efforts.

ESRA continuously updated its administrative structures with the primary goal of enhancing the dissemination of knowledge in RA and, more recently in Pain Management. We can trace the ESRA history step by step, throughout its significant milestones, that are presented below.

·       In 1984, during the Vienna meeting, ESRA established the Carl Koller Award, recognizing Dr John Alfred Lee (UK) as its first recipient. This award, originally sponsored by ASTRA, continues until today to honour, recognize and acknowledge scientific achievements and an outstanding lifetime contribution in the field of RA and/or Pain Medicine.

·       In 1989, ESRA launched its official publication, «The International Monitor of Regional Anaesthesia and Pain Therapy (IMRAPT)», with Mathieu Gielen (The Netherlands) serving as Editor–in–Chief. IMRAPT was initially supported by ASTRA, and later on by ASTRA/ZENECA, with its issues being published on a quarterly basis. Narinder Rawal (Sweden) succeeded Mathieu Gielen, and took over as Editor–in–Chief, holding the position from 1995 to 2005.

·       In 1992, André Van Zundert (Belgium) initiated the publication of the «Highlights» of Regional Anaesthesia and Pain Therapy, serving as Editor–in–Chief until 1999. From 2000 to 2003, he co–edited this edition with Narinder Rawal (Sweden), who then continued as Co–Editor alongside with the society Presidents, Slobodan Gligorijevic (Switzerland) and Giorgio Ivani (Italy), until 2009. In 2010, José de Andres (Spain) and Marc Van De Velde (Belgium) took over as Editors–in–Chief. The Highlights continue to be released as an online RAPM supplement every September.

·       On October 27, 1993, the ESRA Foundation was established, with its statutes being published on December 16, 1993. The foundation's mission was to organize educational activities in RA and Pain Therapy for anaesthetists. Additionally, it was authorized and empowered to grant awards and prizes, to recognize excellence in the fields. 

·       In 1995, the ESRA lecture was introduced, being delivered by JAW Wildsmith (UK), and becoming a prominent feature of the Annual Congresses. 

·       The following year, in 1996, the ASRA lecture was added to the Annual Congress program, with the inaugural lecture being delivered by John Rowlingson (USA).

·       In order to showcase the diverse applications of RA, enhance the understanding and improve the knowledge in the field, as well as to attract new members to join the society, the ESRA Board of Directors planned an International Symposium on RA (ISRA). The inaugural ISRA congress took place in New Zealand from April 9–11, 1996, was supported by ESRA, ASRA, AOSRA, and LASRA, with JFW Wildsmith (UK) being at the helm of its scientific committee.

·       In 1998, during the Annual Congress in Geneva, from September 16–19, the ESRA Board of Directors approved and sanctioned the formation of several new committees. These were:

·a. Newsletter and Promotions Committee (Chair: A. Vadalouca, Greece)

b. Research Grant Committee (Chair: A. Vadalouca, Greece)

c. Education and Website Committee (Chair: B. Fischer, UK)

d. Best Presentation Committee (Chair: M. Gielen, The Netherlands)

e. Guidelines on Acute and Chronic Pain Committee (Chair: N. Rawal, Sweden)

Three prizes for the best free papers and three for the best posters, sponsored by Becton–Dickinson, were awarded for the first time at this meeting. This event also marked the ESRA and EuroPain inaugural joint meeting, followed by another one in Istanbul in 1999. 

Concurrently, the first ESRA Cadaver Workshop in Innsbruck also started that year, with Slobodan Gligorijevic (Switzerland) serving as the chair of this event. This was a significant educational initiative, which was further improved and fine–tuned over the years, remaining one of the most popular ESRA activities until today.

ESRA expanded its global presence and footprint by holding a fruitful international meeting in Jaipur, India, from February 9–13, 1998, with Narinder Rawal (Sweden) being the chair of the event. The society further engaged with and reached out to the Balkan countries, by organizing the 1st Mediterranean and Balkan Congress in Athens, Greece, from June 19-21, 1998, chaired by Athina Vadalouca (Greece), and attracting over 550 participants.

At the Rome ESRA Annual Congress, in 2000, ESRA awarded its first Research Grant, being split between Spanish and Greek recipients. That year, meetings were also held in Quebec and Athens.

In 2002, Barcelona hosted the 1st World Congress of Regional Anaesthesia, providing a global perspective on RA and Pain Therapy. 

The first Eastern European anatomy workshop on RA took place in Ljubljana also in 2002, whereas ESRA launched its first Winter Week course on RA in 2003. Both events were leaded by Slobodan Gligorijevic (Switzerland) and were welcome warmly by their audiences. The Eastern European Cadaver workshops keep being organized, with Paul Kessler (Germany) and Peter Merjavy (UK) serving as event chairs and following a venue rotation between Ljubljana, Prague, and Budapest. Additionally, Winter Week has evolved into an extremely successful activity over the years, being continued until today, under the leadership of Geert Jan Van Geffen (The Netherlands).

The BBraun Award was established in 2005 and was presented to Alain Delbos (France), for his outstanding contribution in UGRA, via the introduction of a 3–D simulation training tool in the format of a DVD. The award kept being sponsored by BBraun until 2010. Afterwards, it was renamed «Recognition of Education in Regional Anaesthesia» Award, and is offered annually to support outstanding innovative activities or developments in the field of RA, as a reflection of excellence in teaching & clinical education. Similarly, the «Recognition of Education in Pain Medicine» Award was introduced in 2023, with Philip Peng (Canada) being its first recipient. 

In 2005, the ESRA Diploma of Regional Anaesthesia (EDRA) was launched, a project driven and spearheaded by André Van Zundert (Belgium), Giorgio Ivani (Italy), Narinder Rawal (Sweden), and Alain Borgeat (Switzerland), with the valuable assistance and substantial contribution from Chandra Kumar (UK). The first EDRA Diploma exams took place, in 2006, during the ESRA Annual Congress in Monte Carlo, Monaco. There were only a few candidates at first (4 in total), but the number has increased considerably since then, with ESRA nowadays counting more than 1000 diplomates. Recently this popular diploma has been renamed to ESRA–DRA (ESRA European Diploma of Regional Anaesthesia).

Education and Excellence in the Provision of Care in Europe and beyond represent an integral part of the ESRA mission. The society is proud of the two jewels on its crown: Not only the ESRA–DRA, but also the ESRA–DPM (ESRA European Diploma of Pain Medicine), which was established in 2017, as an idea of Jose De Andres (Spain). Both aim to harmonize and improve quality standards for safe, independent practice in our fields, in Europe and elsewhere. The Diplomas assess the competencies of anaesthesiologists and pain physicians, acting within a multidisciplinary team and practicing as specialists. They also intend to complement national standards and enhance the competent, ethical, and professional care of RA and Pain Medicine. The ESRA Diplomas Exams, which are quite popular, are organized regularly on an annual basis, remotely and in person, within but also outside the European territory. Both of them, in 2023, during the 6^th World Congress of Regional Anaesthesia and Pain Medicine, have been evaluated and received official accreditation by the Council for European Medical Specialists Assessment (CESMA), an advisory body of the European Union of Medical Specialists (UEMS). Pioneers in this endeavor were Morne Wolmarans (UK) and Sam Eldabe (UK), for the ESRA–DRA and ESRA–DPM respectively.

The ESRA Academy was founded in 2010, was presented at the annual congress in Porto, and was further reformed from scratches in the coming years, being re–launched and presented in 2015 by Paolo Grossi (Italy). The Academy continues to be a valuable tool for all ESRA members, by hosting a variety of online educational content, including but not limited to recorded lectures, videos, and live demonstrations of RA/Pain techniques. 

The updated ESRA bylaws were also presented in 2010, and were approved by the Annual General Assembly, in addition to the «Albert Van Steenberge» Award, which was also launched that year. ESRA kept growing its membership and impact in RA and Pain Therapy in 2013. That year, the first publication on ESRA history by André Van Zundert (Belgium) and JAW Wildsmith (UK) was released and published in the journal RAPM.

In 2014, PROSPECT (Procedure Specific Postoperative Pain Management) and ESRA formalized an agreement to strategize and plan their future partnership and to expand the group membership. PROSPECT, although an ESRA working group, still remains an independent academic body within the society academic umbrella. Currently, under the leadership of Marc Van De Velde (Belgium), continues to benefit from the academic endorsement and support of ESRA and develops some of the best available Consensus Recommendations in a clinically useful format. These are readily transferable in daily practice, serve as a clinical decision support service, and are designed to improve postoperative pain management on a procedure–specific basis. As such, they are translated into multiple languages to be readily available for clinicians across all corners of the world.

In 2014, the 4th World Congress on RA and Pain Therapy (WCRAPT) took place in Cape Town, South Africa, from November 24–28, being jointly organized by ESRA, ASRA, LASRA, and AFSRA.

In 2015, 2016 and onwards, under the leadership of Paul Kessler (Germany), ESRA significantly expanded its accredited workshops, featuring cadaver sessions and practical hands–on training across multiple European cities, mainly Innsbruck and Witten. The cadaver workshops have also expanded in the field of pain and under the guidance of Andrzej Krol (UK), ultrasound and C–Arm facilitated interventional chronic pain techniques are regularly demonstrated and taught. 

In the era of rapid E–Learning transformation, ESRA was a pioneer. It keeps staying in tune with the latest trends and technologies and has adapted the provision of its educational content to the new digitally driven world. Since 2017, it offers its audience access and navigation into the USabcd platform, a unique E–Learning concept, which provides the empowerment one needs with the knowledge of RA and Point–of–Care Ultrasound in clinical practice. Clinicians who utilize the USabcd tool may take advantage of its focused, structured and comprehensive format to improve their diagnosis capabilities and optimize patients’ care in the perioperative, ICU and emergency medicine setting.

At the end of the previous decade, ESRA introduced innovative online educational initiatives, and is proud of its interactive e–Congress (e–ESRA), which was first launched in 2018, by Alain Delbos (France) and Luc Mercadal (France). This internet–based activity, a unique educational concept, brought a new dimension of online education, for a maximum learning outcome. With an extended 24–hour program, broadcasted live all over the world in parallel streams, and the enthusiastic interaction of participants, via live chats, polls & quizzes with instant results, a virtual experience of a full congress, dedicated to RA, Perioperative Care & Pain Medicine, has been accomplished. Its 6^th edition took place in April 2024, under the leadership of Jose Aguirre (Switzerland), with the active involvement of not only ESRA, but also ASRA Pain Medicine, LASRA, AFSRA and AOSRA–PM. It attracted more than 1.200 delegates connected online in one single day, across all continents. Interesting lectures of short duration, podcasts, videos, and Live Demonstration Sessions were presented, and are available for replay, via the ESRA Academy. The e–ESRA represents a hub for elevating education standards and for promoting international collaboration and networking. It opens the doors to knowledge for physicians from Europe and beyond, in a flexible and affordable way, and fosters a diverse and enriching exchange of ideas, transcending any geographical boundaries.

In 2018 and 2019, ESRA was phenomenal in expanding its social media presence and outreach, attracting thousands of followers on platforms like Facebook, Instagram, LinkedIn and Twitter. 

Traditionally, ESRA participated in the development of comprehensive Guidelines or Recommendations on RA and PM practices, in close collaboration with other organizations. The latest ones include, but are not limited to (a) the Joint Guidelines with the European Society of Anaesthesiology and Intensive Care (ESAIC) on how to manage patients on antithrombotic drugs who need RA, published in European Journal of Anaesthesiology in 2022, (b) the International Consensus Meeting (ICM) Recommendations on Venous Thromboembolism (VTE), published in The Journal of Bone and Joint Surgery in 2022, (c) the International Consensus on anatomical structures to identify on ultrasound for the performance of basic blocks in UGRA, published in RAPM in 2022, and (d) the Evidence–Based Clinical Practice Guidelines on Postdural Puncture Headache, as a Consensus Report from a Multisociety International Working Group, published in RAPM and JAMA Open in 2024.

ESRA prioritized education for anaesthetists in training and young specialists across Europe and devotes much of its efforts to the residents, the lifeblood of our profession and the promising future of medical care. Their enthusiasm, fresh perspectives, and unwavering commitment to patient well–being pave the way for innovation and excellence in our fields. Alongside experts’ guidance, ESRA fully supports the ESRA Trainees Group that was created in 2016, and their annual course, whereas a part of the ESRA website educational content is fully dedicated to them. 

Research and Education grants of up to 10.000 and 4.000 EUR each respectively are awarded regularly to young researchers worldwide, who are strongly encouraged to apply. Approved Training Centres of Excellence on RA or/and Pain Medicine in Europe are available to the new generation of physicians, with specific emphasis given to applications from anaesthesiologists from countries lacking the financial infrastructures needed to achieve education in RA and Pain Medicine. The ESRA Updates, the new format of the ESRA Newsletter, initiated by Clara Lobo (Portugal), serves the society by offering content that is not only informative but also engaging for the members. Its main goal and objectives are to spread information on ESRA events and training opportunities and disseminate the spirit of enthusiasm among our younger colleagues. Since May 2016, ESRA, also started offering a Master Diploma (MSc) to its members in partnership with the University of East Anglia.

In 2020 and 2021, ESRA responded to the COVID–19 pandemic by moving many educational events to online formats. Innovative web–based training activities, including free webinars, virtual or hybrid meetings and the well–established e-Congresses (e-ESRA) maintained the society at the knowledge forefront, and finally became tradition. Currently, these tools continue to thrive on an annual basis, showcasing the ESRA dedication to improving RA and Pain Medicine through education, research, and international cooperation.

In 2022, ESRA marked its 40th anniversary since the organization of its first meeting, looking back on its development and achievements in the field. The first annual congress after the pandemic took place in Thessaloniki, Greece, with over 1.750 attendees and more than 500 abstracts, under the leadership of Alain Delbos (France) and Eleni Moka (Greece). The event was both scientifically and socially rewarding.

In 2023, ESRA hosted its biggest scientific event ever, the 6^th World Congress of RA and PM, in Paris, as a joint event with its 40^th Annual Congress. Joining collaborative efforts with all sister societies (ASRA Pain Medicine, AFSRA, LASRA, AFSRA and AORAPM), the impressive numbers of more than 3.300 Delegates, more than 300 Faculty Members & Key Opinion Leaders from all continents, and more than 750 abstracts were achieved. Alain Delbos (France) and Eleni Moka (Greece) led the scientific committee and supervised the whole organization. An expanded, high–quality scientific content was offered to all participants, in parallel with a great family atmosphere, combined with networking, interactivity, knowledge sharing and exchange of new ideas. This congress was not just another ESRA event; it showcased that, in the rapidly evolving landscape of healthcare, deepening partnerships is the cornerstone, upon which we can build bridges, learn from each other, support fundamental changes and establish progress.

ESRA embraces diversity within its community and offers unparalleled networking opportunities and friendships that span the globe. Collective efforts with partners that share similar values and principles are more than welcome, as they enhance the richness of discussions and perspectives, providing a global outlook on our fields. A great example inside ESRA is its International Committee, established in 2021, to give a sound voice to physicians from all continents involved in RA and Pain Medicine. 

The unique experiences and insights of all ESRA followers are not just valued but celebrated! In the past, the highlighting event of such celebration was the European Day of RA, that was first organized in 2018, as an initiative of Alain Delbos (France) and Sebastien Bloc (France) and which continued to take place at the beginning of each year in January, until 2023. Together with the National Societies of RA and Pain Therapy, multiple cities in different European countries every year participated simultaneously, with a common scientific program, aiming at interactivity and exchange of scientific opinions between trainees and experts on hot topics related to RA and Perioperative Care. The primary goal was discussing innovations and combining theory with clinical methodology and Hands–On Practice. With this event, ESRA kept promoting signaling the encouragement of training, education and research in the context of improved quality of continuing medical education among European Anaesthesiologists. 

Following the footsteps of such meetings, and in the same spirit of enthusiasm, ESRA aspired to expand this activity worldwide to contribute to its mission fulfilment. Under the presidency of Eleni Moka (Greece), ESRA, together with its Sister Societies AFSRA, ASRA Pain Medicine, AOSRA and LASRA, launched the 1^st World Week and the 1^st World Day of RA and Pain Medicine in January 2024, drawing more than 14.000 participants from more than 140 cities across all continents. During this week, in the concept of a strengthened alliance, RA and Chronic Pain physicians around the globe were connected together, to shine a spotlight on the critical fields of RA and Pain Medicine, under the inspiring theme “Joining Hands for a Pain Free Future Worldwide”. Recognizing that progress transcends individual achievements, leaders of all RA and PM Sister Societies acknowledged the power of unity, identified shared visions and missions, and recognized the potential for our patients’ benefit.

All ESRA milestones that have been described, allow us to reflect on the progress that has been made and the work that lies ahead. Throughout its remarkable journey, ESRA expanded its horizons and pushed the boundaries to become an international community for everyone who aspires to high standards and professionalism in RA, Perioperative Care and Pain Medicine. Despite challenges, ESRA is a testament to the power of inclusivity and collaboration in our ever–evolving fields of interest. A vibrant tapestry of ideas and shared values were and continue to be created by joining efforts. As we embark on this journey together, let us remember that in unity, we may find strength, and in inclusion, we can discover the boundless potential for growth and innovation. When combined, our individual strengths have the power to collectively achieve remarkable advancements in the pursuit of knowledge, scientific research and patient care. ESRA continues to extend the hand of partnership to everyone that shares its vision, ensuring a brighter future to reach global excellence.

References

1.     André AJ Van Zundert, John AW Wildsmith. The European Society of Regional Anaesthesia and Pain Therapy (1982–2012): 30 Years Strong. Reg Anesth Pain Med, 2013; 38(5): 436 – 441. (The following individuals contributed to this article on behalf of the Heritage Group of the European Society of Regional Anaesthesia and Pain Therapy: Alain Borgeat, MD, PhD, EDRA; José De Andres, MD, PhD, EDRA; Slobodan Gligorijevic, MD, EDRA; Giorgio Ivani, MD, PhD, EDRA; Narinder Rawal, MD, PhD, EDRA, FRCA; Harald Rettig, MD, PhD, EDRA; Athina Vadalouca, MD, PhD; Marc Van De Velde, MD, PhD, EDRA)

2.     ESRA Newsletter, No 1, September 1998.

3.     ESRA Newsletter, No 2, Spring 1999.

4.     The International monitor of Regional Anaesthesia and Pain Therapy, 1992 – 2004.

5.     Highlights in Regional Anaesthesia and Pain Therapy, 1992 – 2010.

6.     Kietaibl S, Ferrandis R, Godier A, Llau J, Lobo C, Macfarlane AJ, Schlimp CJ, Vandermeulen E, Volk T, Von Heymann C, Wolmarans M, Afshari A. Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines. Eur J Anaesthesiol, 2022; 39(2): 100 – 132.

7.     ICM – VTE General Delegates*. Recommendations from the ICM – VTE (Recommendations of the International Consensus Group on Venous Thromboembolism after Orthopaedic Procedures). J Bone Joint Surg Am, 2022; 104(Suppl 1): 4 – 162.

8.     Bowness JS, Pawa A, Turbitt L, Bellew B, Bedforth N, Burckett-St Laurent D, Delbos A, Elkassabany N, Ferry J, Fox B, French JLH, Grant C, Gupta A, Harrop-Griffiths W, Haslam N, Higham H, Hogg R, Johnston DF, Kearns RJ, Kopp S, Lobo C, McKinlay S, Memtsoudis S, Merjavy P, Moka E, Narayanan M, Narouze S, Noble JA, Phillips D, Rosenblatt M, Sadler A, Sebastian MP, Taylor A, Thottungal A, Valdés-Vilches LF, Volk T, West S, Wolmarans M, Womack J, Macfarlane AJR. International consensus on anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia. Reg Anesth Pain Med, 2022; 47(2): 106 – 112.

9.     Uppal V, Russell R, Sondekoppam RV, Ansari J, Baber Z, Chen Y, DelPizzo K, Dirzu DS, Kalagara H, Kissoon NR, Kranz PG, Leffert L, Lim G, Lobo C, Lucas ND, Moka E, Rodriguez SE, Sehmbi H, Vallejo MC, Volk T, Narouze S. Evidence–based clinical practice guidelines on postdural puncture headache: A consensus report from a multisociety international working group. Reg Anesth Pain Med, 2023; Epub online ahead of print – Article in press.

10.  Uppal V, Russell R, Sondekoppam R, Ansari J, Baber Z, Chen Y, DelPizzo K, Dirzu DS, Kalagara H, Kissoon NR, Kranz PG, Leffert L, Lim G, Lobo CA, Lucas ND, Moka E, Rodriguez SE, Sehmbi H, Vallejo MC, Volk T, Narouze S. Consensus Practice Guidelines on Postdural Puncture Headache from a Multisociety, International Working Group: A Summary Report. JAMA Netw Open, 2023; 6(8): e2325387.

11.  ESRA Official Website: www.esraeurope.org [assessed 30^th June 2024].

Key Reasons why Regional Anesthesia is Preferred by Patients, Surgeons and Anesthesiologists

The choice of anesthesia must be tailored to each patient’s specific circumstances and the type of surgery. However, regional anesthesia (RA) offers numerous benefits over general anesthesia (GA) for many surgical patients and has been advocated as a valuable adjunct to a multimodal analgesic regimen. These benefits span across overall experience and patient safety, i.e., improved pain management, higher patient comfort and satisfaction, faster recovery, reduced systemic side effects, and fewer respiratory and cardiovascular complications. 

In terms of environmental impact, RA has several benefits compared to GA: a) complete avoidance of potent anesthetic greenhouse gases results in a decreased atmospheric pollution, a smaller carbon footprint, and reduced long-term pollution; b) lower energy consumption as the patient is in the operating room for a shorter time, requires less monitoring and less electrically-operated medical equipment, and reduces the need for intense ventilation to clear anesthetic gases, which itself engenders significant energy use; c)  RA generates less disposable consumption, leading to less medical waste; d) localized delivery of anesthetic agents reduces the overall quantity of pharmaceuticals entering the environment through patient excretion and drug wastage; e) some equipment used in RA, i.e., nerve stimulators, ultrasound devices, is reusable and has a longer lifespan compared to the single use items often used for GA. One potential environmental downside for RA compared to GA is an increased burden of sterilization and thus electrical consumption. However, this is unlikely to offset the overall environmental benefit of RA.

Some of the key reasons why RA is often preferred include: a) improved pain management: RA provides targeted pain relief at the surgical site, leaving the areas above and below surgery unaffected. Perioperative pain relief is often superior by effectively controlling pain with local anesthetics (LAs), decreasing the need for systemic opioids, thereby lowering the risk of opioid-related side effects and dependency; b) enhanced recovery and mobility: Patients often recover more quickly from RA, experiencing less grogginess and confusion compared to those recovering from GA. This facilitates earlier postoperative mobilization, which is crucial for reducing risks of complications (e.g., deep vein thrombosis) and promoting faster overall recovery; c) fewer respiratory complications due to the avoidance of airway manipulation and preservation of respiratory function: GA requires airway management with its inherent complications (sore throat, hoarseness, and in severe cases, aspiration or respiratory distress). RA avoids these risks by eliminating the need for intubation, preserving the patient’s respiratory function, allowing spontaneous breathing. RA is particularly beneficial for those with existing respiratory conditions; d) cardiovascular stability due to reduced hemodynamic fluctuation: RA typically results in more stable blood pressure and heart rate compared to the hemodynamic changes that can occur with the induction and emergence phases of GA. For patients with cardiovascular conditions, the reduced stress on the heart makes RA a safer option; e) reduced systematic side effects due to the minimized drug exposure and lowered risk of cognitive dysfunction: RA involves less exposure to systemic medications, reducing the risk of drug-related side effects, i.e., nausea and vomiting, and respiratory depression. GA can lead to postoperative cognitive delirium and dysfunction, particularly in the elderly population. RA reduces this risk by avoiding systemic sedatives and anesthetics that affect the brain; f) higher overall patient satisfaction and comfort: RA allows the patients to remain awake or lightly sedated during surgery, allowing them to avoid the disorienting effects of GA; g) RA may not be suitable for all types of surgeries or all types of patients. However, for many complex surgeries that typically require GA, RA can complement by providing excellent pain relief; and h) RA is cost-effective: RA allows faster recovery times which can lead to shorter hospital stays, which is cost-effective for healthcare and the patient. The decreased use of systemic anesthetics and opioids may lower the overall cost of medications.

Whether LAs provide the best perioperative analgesia depends on various factors, including the type of surgery, patient characteristics, and the desired outcomes. LAs provide targeted pain relief by blocking nerve signals in the area of administration, which can be very effective for many surgical procedures using central neuraxial and peripheral nerve blockade, with long-lasting pain relief if catheters are used, often combined with continuous infusion pumps. LAs can be used in various forms, including topical applications, infiltration blockade, nerve blocks, and spinal, epidural or combined anesthesia techniques, making them versatile for different surgical needs.

Limitations of LAs

LAs are highly effective for perioperative pain management, providing targeted analgesia with minimal systemic side effects. However, there are limitations using solely LAs: a) insufficient duration of action: the analgesic effect of LAs is limited to the duration of the block, which may not cover the entire perioperative period. Longer-acting agents, continuous infusion techniques and the use of adjuvants can mitigate these limitations but will add to the complexity of blocks; b) incomplete RA blockade requires supplemental pain management strategies; c) LAs are generally safe but still can cause complications such as LA systemic toxicity (LAST) due to massive resorption or intravascular injections, allergic reactions, or damage to muscles (LA-induced myotoxicity and myo-degeneration), nerves, or spinal cord if improperly administered or when high doses are used.¹

However, their limitations in duration and potential for incomplete pain relief make them most effective when used as part of a multimodal pain management strategy. By combining LAs with other analgesics, adjuvants, and techniques, anesthesiologists can achieve optimal pain control tailored to individual patient needs and surgical contexts.

Adjuvants to LAs

As the indications for RA have gradually expanded, adjuvants are frequently incorporated to enhance patient safety and comfort, improve efficacy, onset, quality and duration of analgesia, reduce the required dose of LAs and minimize potential side effects.^2-6

The benefits of these adjuvants include a faster onset of block, improved hemodynamic stability, reduced postoperative opioid requirements, anti-inflammatory effects, and additional anxiolysis and sedation. These advantages contribute to better pain management, increased patient satisfaction, enhanced clinical outcomes, and improved overall perioperative results. These substances can be added to LAs for various types of regional blocks, including peripheral nerve blocks, fascia blocks, central neuraxial blocks, ophthalmic blocks, and intravenous RA blocks, with the intention of blocking transmission to avoid or relieve pain. Anesthesiologists select these adjuvants based on specific clinical scenarios and surgical interventions, patient-specific factors, type of RA, desired effects, and a balance of their benefits against potential side effects.

Table 1 provides an unrestricted list of potential useful adjuvants to LAs for a variety of RA blocks, including central neuraxial and peripheral nerve blocks. Suggested doses are provided, though clinicians need to verify each dosage according to their local circumstances, the surgical intervention, and the individual patient. LAs and adjuvants are used in a large range of medication types, volumes, doses, and concentrations. It is crucial to consider the appropriate drug in the right volume/concentration/dose for each specific RA technique. Clinicians should evaluate all substances in the correct LA solution for the right indication before any injection. Not all RA adjuvants have been approved by the regulators or licensed for neuraxial administration in all countries, and some preparations may contain additives, such as preservatives that are potentially neurotoxic. In specific clinical circumstances (e.g., existing diabetic neuropathy) some practice modifications may be considered to reduce the risk of overdose, side effects and complications.⁷ Clinicians need to be diligent about monitoring for the development of adverse side effects and complications from LAs and RA adjuvants and their immediate appropriate management. These common side effects limit their clinical use and may pose an even greater threat in certain procedures, including organ damage. 

Opioids act as agonists at G-protein coupled inhibitory receptors, i.e., mu, kappa, delta, and nociceptin. These opioid receptors are widespread throughout the brain (cerebrum, thalamus, hypothalamus, amygdalae, basal ganglia, brainstem, reticular activating system), spinal cord, and non-neural tissues (gastrointestinal tract). Side effects often seen following neuraxial administration of opioids due to their cephalad spread in the CSF or systemic absorption from the epidural space, include pruritus, PONV, urinary retention, and respiratory depression. Minute doses of fentanyl or sufentanil are useful adjuvants to low-dose LAs.^8,9

Adverse effects following the administration of LA mixtures are a concern, including cardiopulmonary, neurological, and renal complications, as well as uncommon reactions such as allergy and rarely malignant hyperthermia. Adjuvants to LAs have their own side effects (see Table 1). Therefore, further research on the development of novel LA adjuvants is necessary.

Liposomal bupivacaine is an example of an extended-release formulation that allows for a slow release of bupivacaine HCl from its liposomes. Another promising avenue is the use of exosomes, a class of new bioactive substances released from specific cells, which show unique effects in repairing damaged tissues and organs.¹⁰Exosomes released from cardiomyocytes after exercise have powerful cardioprotective effects, while those released from mesenchymal stem cells can improve neural cell damage. Exosomes originating from the cerebrospinal fluid can promote neuronal repair processes.  Exosomes may help to overcome the hazards of LA adjuvants, such as cardiovascular, neurotoxic and gastrointestinal risks. Animal research has demonstrated that exosomes derived from different tissue cell sources exhibit repair functions after ischemia-reperfusion injuries, causing cellular metabolic acidosis and short-term organ damage. Exosomes released by specific cell types have been found to exert similar effects as many LA adjuvants. Therefore, these exosomal anesthetic adjuvants can be considered as novel LA adjuvant drugs with additional organ repair functions due to their reduction of the inflammatory response and pain relief. Exosomes exhibit reno-, neuro- and cardioprotective effects and immunosuppressive effects similar to those of stem cells. Reduction of postoperative pain is associated with exosomes of macrophage origin. 

There are numerous aspects of RA adjuvants that were not addressed in this manuscript: a) all adjuvants available for use during RA, i.e., neostigmine and non-steroid anti-inflammatory drugs; b) alternative locally administered analgesic agents that have local anesthetic properties, e.g., tramadol; c) the efficacy of perioperative gabapentin in the treatment of postoperative pain; d) which adjuvants are preferred for specific circumstances e.g., which opioid is superior for a specific RA block; e) adjuvants that are better avoided due to their potential for adverse effects, limited efficacy, or safety concerns, e.g., vasopressin; f) the maximum dosage used in the different blocks; g) the potential of novel local anesthetics with protracted analgesic effect and minimal toxicity, which are neurotoxins isolated from animals, plants, and marine organisms, e.g., α-cobratoxin (α-CTx). The latter is isolated from the Thailand Cobra, which has strong affinity for the α7 subunit of the nAChR (α7nAChR) neuronal receptor of the peripheral nervous system. This neurotoxin leads to the depolarization of postsynaptic membranes and the prevention of neurotransmitter release, hence causing pain relief.

Conclusion

Medications used in anesthesia represent one of the greatest discoveries in medical history, revolutionizing pain management and patient care. The indications for LAs and RA blocks have gradually expanded, often in combination with general anesthesia. When used appropriately, adjuvants can significantly enhance the efficacy of RA, though potential adverse reactions must be carefully managed. These additives may improve the RA block’s quality, onset time, duration, or performance (such as motor blockade). Drugs utilized during RA procedures play a crucial role in perioperative pain prevention and relief.

The growing interest in RA techniques has spurred efforts to extend the duration of LAs. The development of LA adjuvants has been instrumental in mitigating the side effects and complications associated with large doses of LAs, including systemic and neurotoxicity risks. These adjuvants have effectively reduced LA toxicity, improved patient satisfaction, and decreased pain experiences. Adjuvants have also enhanced the speed of recovery, facilitated operator convenience, reduced postoperative delirium and increased the efficiency and safety of RA procedures. Continued research and innovation in new LA adjuvants will further advance the field of anesthesia, offering safer and more effective pain management solutions.

References

1.         Hussain N, McCartney CJL, Neal JM, Chippor J, Banfield L, Abdallah FW. Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis. Br J Anaesth. 2018 Oct;121(4):822-841. doi: 10.1016/j.bja.2018.05.076. PMID: 30236244.

2.         Bao N, Shi K, Wu Y, He Y, Chen Z, Gao Y, Xia Y, Papadimos TJ, Wang Q, Zhou R. Dexmedetomidine prolongs the duration of local anesthetics when used as an adjuvant through both perineural and systemic mechanisms: a prospective randomized double-blinded trial. BMC Anesthesiol. 2022 Jun 7;22(1):176. doi: 10.1186/s12871-022-01716-3. PMID: 35672660; PMCID: PMC9172023.

3.         Martin MTF, Alvarez Lopez S, Aldecoa Alvarez-Santullano C. Role of adjuvants in regional anesthesia: A systematic review. Rev Esp Anestesiol Reanim (Engl Ed). 2023 Feb;70(2):97-107. doi: 10.1016/j.redare.2021.06.006. PMID: 36813032.

4.         Coppens SJR, Zawodny Z, Dewinter G, Neyrinck A, Balocco AL, Rex S. In search of the Holy Grail: Poisons and extended release local anesthetics. Best Pract Res Clin Anaesthesiol. 2019 Mar;33(1):3-21. doi: 10.1016/j.bpa.2019.03.002. PMID: 31272651.

5.         Prabhakar A, Lambert T, Kaye RJ, Gaignard SM, Ragusa J, Wheat S, Moll V, Cornett EM, Urman RD, Kaye AD. Adjuvants in clinical regional anesthesia practice: A comprehensive review. Best Pract Res Clin Anaesthesiol. 2019 Dec;33(4):415-423. doi: 10.1016/j.bpa.2019.06.001. Erratum in: Best Pract Res Clin Anaesthesiol. 2021 Dec;35(4):E3-E4. doi: 10.1016/j.bpa.2020.09.002. PMID: 31791560.

6.         Tresierra S, Gilron I, Mizubuti GB. Adjuvant Medications for Peripheral Nerve Blocks. ATOTW 489, 2023. https://resources.wfsahq.org/anaesthesia-tutorial-of-the-week/

7.         Lirk P, Brummett CM. Regional anaesthesia, diabetic neuropathy, and dexmedetomidine: a neurotoxic combination? Br J Anaesth. 2019 Jan;122(1):16-18. doi: 10.1016/j.bja.2018.09.017. PMID: 30579401.

8.         Dong J, Jin Z, Chen H, Bao N, Xia F. Sufentanil Improves the Analgesia Effect of Continuous Femoral Nerve Block After Total Knee Arthroplasty. J Pain Res. 2023 Dec 7;16:4209-4216. doi: 10.2147/JPR.S409668. PMID: 38090025; PMCID: PMC10712246.

9.         Kim SY, Cho JE, Hong JY, Koo BN, Kim JM, Kil HK. Comparison of intrathecal fentanyl and sufentanil in low-dose dilute bupivacaine spinal anaesthesia for transurethral prostatectomy. Br J Anaesth. 2009 Nov;103(5):750-4. doi: 10.1093/bja/aep263. PMID: 19797249. 

10.   Zhang Y, Feng S, Cheng X, Lou K, Liu X, Zhuo M, Chen L, Ye J. The potential value of exosomes as adjuvants for novel biologic local anesthetics. Front Pharmacol. 2023 Jan 26;14:1112743. doi: 10.3389/fphar.2023.1112743. PMID: 36778004; PMCID: PMC9909291.